Osteoporosis is recognized as a major public health problem in the USA today. Approaching the 21st century, as the "baby boomers" age, the societal impact of osteoporosis will increase. Recognizing the need for a concerted effort to combat this disease, the Federal Government initiated Specialized Centers of Research (SCOR) in Osteoporosis in 1987. Our SCOR brought together a panoply of basic and clinical scientists with the common goal of achieving better understanding of the pathogenesis of osteoporosis, to allow development of innovative treatment regimens. Over the past four years, our SCOR investigators have focused particularly on the roles played by the interplay between parathyroid hormone and sex steroids in the development and treatment of osteoporosis. Our cohesive approach generated a significant amount of new data, and in 1990 allowed initiation of a new therapeutic trial funded by NIH. This current application represents a request for funds to allow these productive studies to continue. The SCOR consists of five projects, each addressing with different approaches our common theme of PTH/estrogen interactions. Project 1 is a basic study which seeks to clarify the cellular mechanisms underlying the effects of PTH and estrogen on osteoclast formation and activity. In Project 2, the ovariectomized rat model is used to gain a better understanding of the mechanisms of estrogen deficiency bone loss, and the role of PTH in its prevention and treatment. Project 3 brings a new dimension to our SCOR with studies of electromechanical forces, and in particular their interaction with the PTH/estrogen systems in the development and reversal of bone loss. Project 4 utilizes the paradigm of primary hyperparathyroidism in postmenopausal women to gain further insights into PTH/estrogen interactions on skeletal homeostasis. Project 5 is a continuation of a randomized, controlled trial of the efficacy of combined estrogen and PTH administration in the treatment of established osteoporosis. Each of these projects relies heavily on the support of four "Core" units: Administration/Statistics; Biochemistry; Bone Histomorphometry; and Bone Mass Measurement.